The Cross-Border Biotech Blog

Biotechnology, Health and Business in Canada, the United States and Worldwide

Tag Archives: Ontario Institute for Cancer Research

Monday Biotech Deal Review: November 14, 2011

Welcome to your Monday Biotech Deal Review for November 14, 2011, marking the end of its one month hiatus.  The Monday Biotech Deal Review will now be resuming its normal weekly schedule.  Below are summaries of recent transactions over the past month, which includes the acquisition of Afexa by Valeant for $0.85 per Afexa share, in cash.    Read on to learn more.  Read more of this post

Friday Science Review: March 11, 2011

Insulin + Pancreatic Stem Cells, Proof of Life

University of Toronto ♦ Published in Cell Stem Cell, Mar. 4, 2011

The origin of insulin-producing pancreatic β-cells has been a matter of contentious debate. Some research groups have produced findings that would suggest β-cells duplicate themselves and that new β-cells do not arise from the differentiation of a more primitive pancreatic progenitor. Other groups have proven the existence of pancreas-derived multipotent progenitors (PMPs) that are capable of giving rise to a spectrum of cells from both the pancreatic and neural lineage. So where do β-cells come from?

New results from the lab of Dr. Derek van der Kooy point in the direction of PMPs. Lineage labeling experiments in mice showed that PMPs originate from the embryonic pancreas, as opposed to the neural crest, which has often been cited as the source of pancreatic progenitors. These findings are in conflict with previous studies which could not provide evidence of pancreatic progenitors in the developing embryo or the adult. Convincingly, Dr. van der Kooy’s group was able to show that PMPs express insulin in vivo, an attribute that has often been considered prerequisite for the production of β-cells.

Analysis of human islet tissue showed that PMPs also exist in humans, and, similar to the mouse PMPs under observation, were capable of differentiation to both the pancreatic and neural lineages. Both mouse and human PMPs were able to alleviate diabetic conditions in mice and may provide another avenue to explore in the pursuit of therapeutic cells for transplantation therapy.

Selective Pressures Shape the Genomic Integrity of Human iPS Cells During Reprogramming

Samuel Lunenfeld Research Institute ♦ Ontario Institute for Cancer Research ♦ The Hospital for Sick Children ♦ University of Toronto

Published in Nature, Mar. 3, 2011

Coercing fibroblasts to revert to an embryonic stem cell-like state places a good deal of stress on the genome. The consequences of reprogramming can affect the development of safe populations of cells for therapeutics, which is why researchers at the Samuel Lunenfeld Research Institute have been interested in understanding how the reprogramming process affects genomic integrity. The integrity of a genome can be measured using copy number variation (CNV) within a population of cells. CNVs arise from deletions or duplications in DNA; as variation increases, the integrity of the genome declines.

In this study supervised by Dr. Andras Nagy and Dr. Timo Otonkoski, researchers characterized the CNV content of 22 human iPS cell lines and 17 human ES cell lines using Affymetrix SNP arrays. Induced pluripotent cell lines were created by way of retroviral transduction or with the use of a transposon known as piggybac. The number of CNVs in iPS cells was roughly twice that found in ES cells on average and many CNVs found in iPS cells were undetectable in ES cells suggesting that CNVs are generated during the reprogramming process. To the surprise of the group the number of CNVs in iPS cells was greatest at early stages, and decreased as cells were passaged in culture.

Researchers hypothesized that the reduction in copy number variation could be the result of two things, firstly, a DNA repair mechanism that corrects deletions and additions as the cells grow and divide in vitro, or mosaicism in early cultures followed by selection of iPS cells that have lower variation and greater genomic stability; a survival of the fittest in a way. It is unlikely that a DNA repair mechanism could operate fast enough to account for the rapid reduction of CNVs observed in iPS cells in culture and indeed, after using fluorescence in situ hybridization (FISH), it was confirmed by the lab group that mosaicism did exist in early cultures of iPS cells. In order to prove that selection was driving the decrease in CNVs researchers focused on deletions that cannot be corrected by DNA repair mechanisms. They found that several of these deletions were selected against during passaging of iPS cell lines. This pressure was bidirectional however, as some CNVs were selected for, not against.

CIITA, A Promiscuous Partner in Lymphoid Cancers

Centre for Translational and Applied Genomics ♦ BC Cancer Agency ♦ University of British Columbia

Published in Nature, Mar. 2, 2011

Chromosomal translocation events are a common abnormality leading to the development of cancer but few have been described as contributors to the development of lymphoid cancers. A new chromosomal translocation event has been implicated in the development of Hodgkin lymphoma and primary mediastinal B-cell lymphoma (PMBCL). Large scale mutations of this nature occur when non-homologous chromosomes transiently stick together and cause breakages that lead to the exchange of genetic information. If genes are placed next to one another following the translocation event, fusion transcripts are created which can lead to cellular abnormalities and malignant expansion.

Genome-wide mapping of translocation events can be carried out using paired-end sequencing of expressed transcripts. Researchers used such a platform to analyze two Hodgkin lymphoma cell lines. Analysis uncovered a highly expressed gene fusion between the MHC class II complex (CIITA) and an uncharacterized gene. Further analysis of 263 B-cell lymphoma cell lines went on to show that the CIITA translocation was highly recurrent in PMBCL (38%) and Hodgkin lymphoma (15%). The genetic event appears to be quite specific to PMBCL as it was observed in only 3% of diffuse large B-cell lymphoma cell lines.

Researchers note that although certain translocation events of very specific rearrangements are key contributors to some B-cell lymphomas, resulting in unique clinopathological features, many well characterized B-cell lymphomas still lack identifiable translocations that define the disease. Translocations in B-cell lymphomas are a rare occurrence, and until the publication of this research, no translocations had ever been reported in PMBCL.

Monday Biotech Deal Review: May 3, 2010

I guess the excitement of BIO was driving deals this week. To the delight of the economic development folks, government was in on the action — Ontario announced a BIP investment and announced a whole new strategy, and OICR funded three equity deals. The private sector was also out in force, with four new licensing deals (including some interesting structures) and more securities than the week might otherwise … warrant. Keep reading after the jump…

Monday Biotech Deal Review: April 12, 2010

This week deals are back in full force, despite the fact that Tengion’s IPO was less popular than expected and Neovacs scaled back its planned IPO.  Highlights include Patheon raising $280 million from its note placement, Verio Therapeutics getting phagocytosed by Fate (but remaining in Ottawa) and Lorus Therapeutics’ F-1 filing for a $17.5 million unit offering. Read more of this post

Monday Biotech Deal Review: March 22, 2010

Bought deals are all the rage this week, with BioExx and Osta Biotechnologies both heading in that direction.  Also, everywhere we look, warrants are being exercised and debentures are being converted. We even noted the green shoots of a new Canadian listed biotech company poking through the ground via a CPC transaction.  Is there a Spring thaw in Canada’s biotech capital markets?  Read more of this post

Boosting Canadian Commercialization at the Ontario Institute of Cancer Research

Alex Philippidis ran a great story at GenomeWeb last week on the OICR’s plans for 2010, which include hiring 40 more staff, growing informatics capabilities and providing additional support for its Intellectual Property Development and Commercialization program.

On the commercialization front, the news is particularly exciting.  OICR has already been willing to participate in novel initiatives like POP-CURE, and has now hired two executives with extensive industry experience:

Franklin Stonebanks, the new chief commercial officer, “founded global life-science advisory firm Blackcomb Advisors; served as president and CEO of Cynvec; and held managerial positions in the venture funds of Johnson & Johnson and IBM, where he also led its healthcare and life science mergers-and-acquisitions effort.”

Nicole Onetto, the new deputy director, was “senior VP and chief medical officer of ZymoGenetics, and earlier served as executive VP and chief medical officer of OSI Pharmaceuticals. She was international project leader for Taxol, and led the clinical development of Tarceva (erlotinib) for non-small cell lung cancer and pancreatic cancer in collaboration with the National Cancer Institute of Canada.”

The OICR team has already invested over $5 million in 12 startups, three of which have since been acquired.  The funded projects include imaging technologies, biomarkers and new therapeutics.  These two should be great additions, and together with Rafi Hofstein, are raising the international profile of Canadian innovation.

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Pfizer and Ontario BIP Program Funding New $6.9 million “POP-CURE” Project for Colorectal Cancer Genomics

B&W_DNA_sequence Pfizer Global Research and Development is contributing $6 million and the Ontario government is contributing $900,000, through the Biopharmaceutical Investment Program (BIP), for a new project “to discover and validate new targets for the diagnosis, prognosis and treatment of colorectal cancer.”  Brad Wouters, a Senior Scientist with the Ontario Cancer Institute (OCI) and a Senior Investigator at the Ontario Institute for Cancer Research (OICR), will lead the project.

Here’s the scoop from the OICR press release:

“Dr. Wouters and a team of scientists at OCI and OICR will use genomic and molecular pathology approaches and develop a large clinical biobank to identify molecular signatures in colorectal cancer. These molecular signatures will be used to accelerate the development of biomarkers for early detection, monitoring and treatment of cancer.”

The Canadian Press article includes some additional background info on the project, which Paul Lévesque, president of Pfizer Canada, says began with a trip by Ontario researchers to meet Pfizer scientists in San Diego almost two years ago.

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